The goals of this project are to elucidate the mechanisms of action of tumor viruses and to determine the cellular alterations responsible for naturally occurring human malignancies. Topics of present interest include: (1) transforming genes of retroviruses and cancer cells; (2) the biology of endogenous retroviruses; (3) the molecular biology of retrovirus replication and transformation; and (4) the application of knowledge gained from these studies to the search for the causes and mechanisms involved in human neoplastic transformation. Some of the most important insights have been developed in the past year. LCMB's accomplishments include: characterization of oncogenes in a number of human cancers and their homologies with defined oncogenes of transforming retroviruses; identification of genetic lesions responsible for activating proto-oncogenes of onc genes into transforming genes as single base alterations which change single amino acids within the proteins coded by the gene; identification of onc genes activated by carcinogen-induced tumors in model systems; mapping the chromosomal locations of a number of onc genes in the human genome and demonstrating the specific rearrangement of one of these genes in translocations associated with Burkitt's lymphoma; detection of the products of previously unidentified onc genes and characterization of their functions.